Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate

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It has been reported from our laboratories that expression of CYP2E1 significantly increased and decreased in rats with acute renal failure induced by uranyl nitrate (U-ARF) treated with recombinant human growth hormone (rGH) for one day (U-ARF1) compared with those in control rats and rats with U-ARF, respectively. Chlorzoxazone (CZX) primarily undergoes hydroxylation to form 6-hydroxychlorzoxazone (OH-CZX) catalyzed mainly by CYP2E1 in rats. Hence, the effects of rGH on the pharmacokinetics of intravenous CZX (20 mg/kg) were investigated in rats with U-ARF. Based on CYP2E1 expression, it could be expected that in rats with U-ARF1, the formation of OH-CZX significantly increased and decreased compared with those in control rats and rats with U-ARF, respectively. This was proven in the following results. First, the total area under the plasma concentration-time curve from time zero to 8 hr (AUC(0-->8 hr)) of OH-CZX in rats with U-ARF1 (36100 mug min/ml) was significantly greater and smaller than those in control rats (1040 mug min/ml) and rats with U-ARF (50300 mug min/ml), respectively. Second, the AUC(0-->8 hr), (OH-CZX)/AUC(CZX) ratio in rats with U-ARF1 (28.9) was significantly greater and smaller than those in control rats (0.468) and rats with U-ARF (72.6), respectively. (C) 2003 Elsevier Science Inc. All rights reserved.
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Issue Date
2003-06
Language
English
Article Type
Article
Keywords

PROTEIN-CALORIE MALNUTRITION; CYTOCHROME-P450 2E1; DOSAGE REGIMENS; PLASMA; 6-HYDROXYCHLORZOXAZONE; HYDROXYLATION; METABOLISM; CLEARANCE; BINDING; DRUGS

Citation

LIFE SCIENCES, v.73, no.3, pp.253 - 263

ISSN
0024-3205
DOI
10.1016/S0024-3205(03)00268-6
URI
http://hdl.handle.net/10203/206036
Appears in Collection
BS-Journal Papers(저널논문)
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